Ionic homeostasis in the rat brain was examined by measuring chloride (C1) transport at the blood-brain barrier under different experimental conditions. Plasma (C1) of pentobarbital-anesthetized rats was varied acutely between 114 mM and 16 mM by means of peritoneal dialysis. Thereafter, constant C1 concentrations were maintained by bilateral nephrectomy. The blood to brain transfer constant (k) of C1 was determined in different brain regions by measuring brain radioactivity at 30 min after the radioisotope, C136, was injected intravenously. The transfer constant varied 2-fold in the range of C1 concentrations examined, and could be described by saturation (Michaelis-Menton) kinetics. Monovalent anions competitively inhibited C1 movement into the brain. The concentration dependence of C1 uptake, and inhibition by monovalent anions, indicate that C1 crosses the blood-brain barrier by a carrier mediated mechanism.